Technetium-99m-dimercaptosuccinic acid renal scintigraphy in children over 5 years

We retrospectively evaluated the frequency of renal scintigraphic abnormalities in children over 5 years admitted with a first symptomatic urinary tract infection (UTI). Among 261 children investigated, we found only 23 over 5 years having had technetium-99m-dimercaptosuccinic acid scintigraphy during the acute phase of a first UTI. Obvious scintigraphic abnormalities were detected in 14 children (15 kidneys): 12 kidneys showed focal cortical defects and 3 were small and deformed. Ultrasound was normal in 7 of the 15 kidneys with abnormal scintigraphy and in all the kidneys with normal scintigraphy. Among the 12 kidneys with focal cortical lesions, 8 kidneys returned to normal or improved considerably 2-12 months after initial work-up. In conclusion, in children over 5 years admitted with a first symptomatic UTI, the frequency of scintigraphic abnormalities is high and a strategy based only on ultrasound data would miss about 50% of the abnormal kidneys.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Preimplantation diagnosis for fragile X syndrome based on the detection of the non-expanded paternal and maternal CGG

Fragile X syndrome is the most common monogenic cause of mental retardation in boys. It is always characterized clinically by moderate mental retardation and often by a long face with large everted ears and macro-orchidism. The causal mutation is an expansion of a CGG triplet repeat in a 5' exon of the FMR-1 gene in Xq27.3. We report here for the first time a method for preimplantation genetic diagnosis (PGD) for fragile X syndrome based on the amplification of the CGG triplet in the normal allele. Our candidate-patient population, as well as two clinical preimplantation genetic diagnosis (PGD) cycles which led to a pregnancy with an unaffected fetus, are presented in this paper.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

A 2-year multicentre, open-label, randomized, controlled study of growth hormone (Genotropin(®) ) treatment in very young children born small for gestational age: Early Growth and Neurodevelopment (EGN) Study

OBJECTIVE In Europe, growth hormone (GH) treatment for children born small for gestational age (SGA) can only be initiated after 4 years of age. However, younger age at treatment initiation is a predictor of favourable response. To assess the effect of GH treatment on early growth and cognitive functioning in very young (<30 months), short-stature children born SGA. DESIGN A 2-year, randomized controlled, multicentre study (NCT00627523; EGN study), in which patients received either GH treatment or no treatment for 24 months. PATIENTS Children aged 19-29 months diagnosed as SGA at birth, and for whom sufficient early growth data were available, were eligible. Patients were randomized (1:1) to GH treatment (Genotropin(®) , Pfizer Inc.) at a dose of 0·035 mg/kg/day by subcutaneous injection, or no treatment. MEASUREMENTS The primary objective was to assess the change from baseline in height standard deviation score (SDS) after 24 months of GH treatment. RESULTS Change from baseline in height SDS was significantly greater in the GH treatment vs control group at both month 12 (1·03 vs 0·14) and month 24 (1·63 vs 0·43; both P < 0·001). Growth velocity SDS was significantly higher in the GH treatment vs control group at 12 months (P < 0·001), but not at 24 months. There was no significant difference in mental or psychomotor development indices between the two groups. CONCLUSIONS GH treatment for 24 months in very young short-stature children born SGA resulted in a significant increase in height SDS compared with no treatment

Preimplantation genetic diagnosis for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Sickle cell disease from Africa to Belgium, from neonatal screening to clinical management.

To describe the severity of sickle cell disease (SCD) in newborns in Belgium and evaluate the impact of neonatal screening (NS) on clinical outcome.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Clinical application of preimplantation genetic diagnosis for cystic fibrosis

Cystic fibrosis (CF) is an autosomal recessive disease characterized by obstruction and chronic infections of the respiratory tract and pancreatic insufficiency. The gene was cloned in 1989 and the most frequent mutation was shown to be the ΔF508 mutation. During PGD, embryos obtained in vitro are checked for the presence or absence of the mutation, after which only embryos shown to be free of the mutation are returned to the mother. Up to 1999, 48 intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF) cycles had been carried out for PGD for CF in 24 couples, and different diagnostic tests had been used to select non-affected embryos. Thirteen patients became pregnant and 12 healthy babies have been born. Copyright (C) 2000 John Wiley and Sons, Ltd.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Low Sickle Cell Disease Mortality In Belgium and Benefit From Hydroxyurea Therapy

In Western countries, mortality among patients with sickle cell disease (SCD) has decreased in the last decades by means of neonatal screening (NS), infectious prophylaxis and care improvements. The major causes of death in children include acute chest syndrome, sepsis, splenic sequestration, stroke, aplastic crisis while in adults end-stage organ failure contributes also to premature death. Hydroxyurea (HU) and stem cell transplantation (SCT) are used in Belgium for more than 20 years but their possible influences on survival have not been yet analyzed. The Belgian SCD Registry was created in 2008 including patients of 8 centres. All available data in 2008 were retrospectively encoded in the database. After 2008 and until 2012, all data were recorded prospectively for already registered patients as well as newly diagnosed subjects. Data were registered from NS or from diagnosis (first contact) until last follow up (FU) visit, SCT or death. Data included diagnosis, demography and outcome data. After SCT, only vital status and cause of death were recorded. Up to date, data from 470 pts are recorded (224 males), 412 are HbSS, 14 HbSβ0, 7 HbSβ+ and 37 HbSC. The median age at diagnosis and at last FU was respectively 0.7 year (y) and 9.9 y. The FU for the whole cohort was 3810 patient-years (PY) and with 136 patients aged over 18y, their FU during adulthood accounted for 520 PY. Thirteen patients died (2.8%). The mortality per 100-PY was 0.34 and the median age at death was 14.5 y (range, 1.5-23.7 y). All deaths occurred in HbSS patients, 5 after SCT and 8 due to an acute event. Complete data set is missing for 3 of the 8 patients. For the 5 well documented SCD related deaths, causes were: hemorrhagic stroke (2), sepsis due to S. pneumoniae (1), aplastic crisis (1) and infection during stay in homeland (1). At last FU, 91 patients were transplanted, 182 were on HU, 7 on HU + chronic transfusion (CT), 19 on CT (4 after HU treatment). The remaining 171 patients never had disease modifying therapy (DMT). Compared with the latter, mortality rate for those on HU was significantly reduced (0.1 vs 0.5/100-PY) while patients on HU have longer FU and are older at last FU (Table 1). Among 91 patients transplanted at a median age 6.9 y, 5 died: 3 from acute transplant related toxicity, 1 from secondary acute myeloblastic leukemia after cGVHD, and 1 is unexplained more than 7 years post SCT. The data issued from the most recent NS cohorts report a low death rate during childhood ranging from 0.13 to 0.52. Even if our Belgian cohort is not exclusively issued from neonatal diagnosis, the observed death rate is low (0.34/100-PY). Several methodological biases are present in this partially retrospective study (incomplete or unavailable data, lost of FU, no information if death occurred before the first contact in a center, …). Nevertheless our low mortality is not underestimated since 1) most patients were followed since infancy and during a long period (3810 PY); 2) the FU during adulthood (period of increased mortality) accounted for 520 PY; 3) our cohort represents a very large part of the Belgian SCD population since a national inquiry performed in 2007 estimated the whole SCD population to 500. The effect of HU on mortality has been reported in adults and more recently in children. Despite longer FU and older age at last FU, our data confirms those previously results. With only one case, death by infection is rare while SCT complications contributed to about 40 % of deaths. Even if SCT is the only curative option for SCD, it encompasses a risk of mortality. As life expectancy of SCD patients has been extended which is confirmed by our results (especially for patients on HU), SCT should be reserved for clinically severe cases. Population-based prospective studies evaluating the survival in transplanted and non transplanted patients are needed

Genetic Counseling in Hemoglobin SC Disease: Data from the Belgian Registry

peer reviewedaudience: professional, studen

An estimation of the incidence and demographic picture of the major hemoglobinopathies in Belgium (from a confidential inquiry).

An estimation of the incidence and demographic picture of the major hemoglobinopathies in Belgium has been approached through a confidential inquiry sent to 228 pediatric and adult hematological departments. Forty-two percent of responses showed that 417 patients are known in Belgium: 83% with sickle cell disease, 13% with beta-thalassemia (beta-thal) major, 2% with beta-thal intermedia, and 1% with Hb H disease. Twenty-five percent of the sickle cell disease patients and 54% of those suffering from a beta-thal major were older than 20 years. Three hospitals ensure the follow-up of 70% of the patients and are situated in Brussels, Belgium; a follow-up of less than 20 patients was reported at 21 centers. These results confirm that sickle cell disease is the major hemoglobinopathy in Belgium; it concerns mostly pediatricians but adult hematologists are also confronted with these pathologies. Therefore, it is necessary to implement integrated programs of prevention and treatment.Journal ArticleMulticenter StudyResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe